Phagocytic cells serve as scavengers, disposing of abnormal cells recognized by the organism as not-self (e.g., malignant cells), microorganisms, and miscellaneous particulate matter. We propose to investigate the manner in which these cells act upon the material they ingest. Two aspects of phagocytic cell function will be studied. The first aspect concerns the role of superoxide in the function of the granulocyte. Using the inhibition of cytochrome C reduction by superoxide dismutase as a diagnostic tool, superoxide production by normal and leukemic granulocytes and by granulocytes from patients with familial defects in white cell function will be studied. Cell-free homogenates of granulocytes will be used to investigate the properties of the superoxide-generating system. The existence of granulocyte superoxide dismutase will be sought. The role of superoxide in the bactericidal activity of granulocytes will be investigated by measuring the effect of dismutase on bacterial killing by these cells. The second aspect concerns the degradation by peritoneal macrophages and Kupffer cells of mammalian cell membrane and bacterial cell wall constituents. Using artificial substrates, the spectrum and properties of the glycosidase activities of these cells will be surveyed. Natural substrates, including group-specific glycolipid present in the membranes of red cells and human adenocarcinoma cells, and lipopolysaccharide and peptidoglycan from bacteria, will then be prepared and their degradation measured. With a mutant of E.coli whose cell wall can be specifically labeled with C14, the relationship between cell wall degradation and the bactericidal activity of the macrophages will be investigated. The effect of prior phagocytosis on the cellular levels of the above-mentioned activities will be studied.